Abstract
The N-methyl-D-aspartate (NMDA) receptor contributes to synaptic plasticity in the central nervous system and is both serine-threonine and tyrosine phosphorylated. In CA1 pyramidal neurons of the hippocampus, activators of protein kinase C (PKC) as well as the G-protein-coupled receptor ligands muscarine and lysophosphatidic acid enhanced NMDA-evoked currents. Unexpectedly, this effect was blocked by inhibitors of tyrosine kinases, including a Src required sequence and an antibody selective for Src itself. In neurons from mice lacking c-Src, PKC-dependent upregulation was absent. Thus, G-protein-coupled receptors can regulate NMDA receptor function indirectly through a PKC-dependent activation of the non-receptor tyrosine kinase (Src) signaling cascade.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Alkaloids
-
Amino Acid Sequence
-
Animals
-
Benzophenanthridines
-
Cells, Cultured
-
Enzyme Activation / drug effects
-
Enzyme Inhibitors / pharmacology
-
GTP-Binding Proteins / physiology*
-
Genistein / pharmacology
-
Isoflavones / pharmacology
-
Lysophospholipids / pharmacology
-
Mice
-
Mice, Knockout
-
Microinjections
-
Molecular Sequence Data
-
Muscarine / pharmacology
-
Nerve Tissue Proteins / physiology*
-
Neuronal Plasticity
-
Oocytes / drug effects
-
Oocytes / metabolism
-
Patch-Clamp Techniques
-
Phenanthridines / pharmacology
-
Phenols / pharmacology
-
Phosphorylation
-
Protein Kinase C / antagonists & inhibitors
-
Protein Kinase C / physiology*
-
Protein Processing, Post-Translational
-
Proto-Oncogene Proteins pp60(c-src) / antagonists & inhibitors
-
Proto-Oncogene Proteins pp60(c-src) / deficiency
-
Proto-Oncogene Proteins pp60(c-src) / genetics
-
Proto-Oncogene Proteins pp60(c-src) / physiology*
-
Pyramidal Cells / drug effects*
-
Pyramidal Cells / physiology
-
Rats
-
Rats, Wistar
-
Receptors, Cell Surface / drug effects
-
Receptors, Cell Surface / physiology*
-
Receptors, G-Protein-Coupled*
-
Receptors, Lysophosphatidic Acid
-
Receptors, Muscarinic / drug effects
-
Receptors, Muscarinic / physiology*
-
Receptors, N-Methyl-D-Aspartate / physiology*
-
Salicylates / pharmacology
-
Signal Transduction / drug effects
-
Signal Transduction / physiology*
-
Tetradecanoylphorbol Acetate / chemistry
-
Tetradecanoylphorbol Acetate / pharmacology
-
Xenopus laevis
-
meta-Aminobenzoates
Substances
-
Alkaloids
-
Benzophenanthridines
-
Enzyme Inhibitors
-
Isoflavones
-
Lysophospholipids
-
Nerve Tissue Proteins
-
Phenanthridines
-
Phenols
-
Receptors, Cell Surface
-
Receptors, G-Protein-Coupled
-
Receptors, Lysophosphatidic Acid
-
Receptors, Muscarinic
-
Receptors, N-Methyl-D-Aspartate
-
Salicylates
-
meta-Aminobenzoates
-
lavendustin B
-
lavendustin A
-
daidzein
-
Muscarine
-
Genistein
-
chelerythrine
-
Proto-Oncogene Proteins pp60(c-src)
-
Protein Kinase C
-
GTP-Binding Proteins
-
Tetradecanoylphorbol Acetate